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Candesartan prevents L-NAME-induced cardio-renal injury in spontaneously hypertensive rats beyond hypotensive effects

Groupe Rein et Hypertension, Institut Universitaire de Recherche Clinique, Montpellier, France, casellas{at}iurc1.iurc.montp.inserm.fr

Abderraouf Herizi

Groupe Rein et Hypertension, Institut Universitaire de Recherche Clinique, Montpellier, France

Annie Artuso

Groupe Rein et Hypertension, Institut Universitaire de Recherche Clinique, Montpellier, France

Albert Mimran

Groupe Rein et Hypertension, Institut Universitaire de Recherche Clinique, Montpellier, France

Bernard Jover

Groupe Rein et Hypertension, Institut Universitaire de Recherche Clinique, Montpellier, France

Our goal was to assess the cardiovascular and renal protection afforded by angiotensin II type 1-receptor blockade against N^G-nitro-L-arginine methyl ester (L-NAME)-exacerbated hypertension in young spontaneously hypertensive rats (SHR), in comparison with the antihypertensive drug, hydralazine. Male SHR were assigned to four groups (n=8 per group): no treatment (controls); L-NAME-treated group (20 mg/kg/day, 10 days, orally); co-treatment with L-NAME and hydralazine (15 mg/kg/day, by gavage); co-treatment with L-NAME and candesartan cilexetil (10 mg/kg/day, by gavage), i.e. at a dose that inhibited acute pressor responses to 5—20 ng angiotensin II. One animal died in the L-NAME group, and tail-cuff systolic blood pressure (SBP) increased significantly compared with controls to 201±5 mmHg. Albumin excretion increased 235-fold in L-NAME-treated rats. Heart weight index averaged 3.5±0.1 and 3.8±0.1 mg/g body weight (p<0.05) in control and L-NAME rats, respectively, indicating moderate cardiac hypertrophy induced by L-NAME. Preglomerular vascular lesions affected 63±6% of interlobular arteries and 10±2% of afferent arterioles (vs. 8±3 and 0.8±0.4% in controls, respectively). Hydralazine and candesartan cilexetil treatment similarly reduced SBP to 153±7, and 165±6 mmHg, respectively. However, candesartan provided more protection, in terms of no significant change in albuminuria (vs. 25-fold increase with hydralazine), regression of cardiac hypertrophy, frequency of vascular lesions and histological indices of renal injury maintained within control values. In conclusion, candesartan cilexetil prevented L-NAME-exacerbated hypertension and associated cardio-renal injury in young SHR, the beneficial effects exceeding those of hydralazine.

Key Words: cardiac hypertrophy • arterial remodelling • glomerular injury • interstitial fibrosis • vascular injury

Journal of Renin-Angiotensin-Aldosterone System, Vol. 2, No. 1 suppl, S84-S90 (2001)
DOI: 10.1177/14703203010020011501


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